PMID- 35281898
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220510
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Human N-Acetyltransferase 1 and 2 Differ in Affinity Towards Acetyl-Coenzyme A 
      Cofactor and N-Hydroxy-Arylamine Carcinogens.
PG  - 821133
LID - 10.3389/fphar.2022.821133 [doi]
LID - 821133
AB  - Arylamine N-acetyltransferases catalyze the transfer of acetyl groups from the 
      endogenous cofactor acetyl coenzyme A (AcCoA) to arylamine (N-acetylation) and 
      N-hydroxy-arylamine (O-acetylation) acceptors. Humans express two arylamine 
      N-acetyltransferase isozymes (NAT1 and NAT2) which catalyze both N- and 
      O-acetylation but differ in genetic regulation, substrate selectivity, and 
      expression in human tissues. We investigated recombinant human NAT1 and NAT2 
      expressed in an Escherichia coli JM105 and Schizosaccharomyces pombe expression 
      systems as well as in Chinese hamster ovary (CHO) cells to assess the relative 
      affinity of AcCoA for human NAT1 and NAT2. NAT1 and NAT2 affinity for AcCoA was 
      higher for recombinant human NAT1 than NAT2 when catalyzing N-acetylation of 
      aromatic amine carcinogens 2-aminofluroene (AF), 4-aminobiphenyl (ABP), and 
      beta-naphthylamine (BNA) and the metabolic activation of N-hydroxy-2-aminofluorene 
      (N-OH-AF) and N-hydroxy-4-aminobiphenyl (N-OH-ABP) via O-acetylation. These 
      results suggest that AcCoA level may influence differential rates of arylamine 
      carcinogen metabolism catalyzed by NAT1 and NAT2 in human tissues. Affinity was 
      higher for NAT2 than for NAT1 using N-OH-AF and N-OH-ABP as substrate consistent 
      with a larger active site for NAT2. In conclusion, following recombinant 
      expression in bacteria, yeast, and CHO cells, we report significant differences 
      in affinity between human NAT1 and NAT2 for its required co-factor AcCoA, as well 
      as for N-hydroxy-arylamines activated via O-acetylation. The findings provide 
      important information to understand the relative contribution of human NAT1 vs 
      NAT2 towards N-acetylation and O-acetylation reactions in human hepatic and 
      extrahepatic tissues.
CI  - Copyright (c) 2022 Hein, Doll and Habil.
FAU - Hein, David W
AU  - Hein DW
AD  - Department of Pharmacology and Toxicology, University of Louisville School of 
      Medicine, Louisville, KY, United States.
FAU - Doll, Mark A
AU  - Doll MA
AD  - Department of Pharmacology and Toxicology, University of Louisville School of 
      Medicine, Louisville, KY, United States.
FAU - Habil, Mariam R
AU  - Habil MR
AD  - Department of Pharmacology and Toxicology, University of Louisville School of 
      Medicine, Louisville, KY, United States.
LA  - eng
GR  - P20 GM113226/GM/NIGMS NIH HHS/United States
GR  - P30 ES030283/ES/NIEHS NIH HHS/United States
GR  - P42 ES023716/ES/NIEHS NIH HHS/United States
GR  - P50 AA024337/AA/NIAAA NIH HHS/United States
PT  - Journal Article
DEP - 20220225
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8914035
OTO - NOTNLM
OT  - N-acetylation
OT  - O-acetylation
OT  - acetyl coenzyme A
OT  - affinity
OT  - arylamine N-acetyltransferase 1
OT  - arylamine N-acetyltransferase 2
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/03/15 06:00
MHDA- 2022/03/15 06:01
PMCR- 2022/02/25
CRDT- 2022/03/14 05:28
PHST- 2021/11/23 00:00 [received]
PHST- 2022/01/24 00:00 [accepted]
PHST- 2022/03/14 05:28 [entrez]
PHST- 2022/03/15 06:00 [pubmed]
PHST- 2022/03/15 06:01 [medline]
PHST- 2022/02/25 00:00 [pmc-release]
AID - 821133 [pii]
AID - 10.3389/fphar.2022.821133 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Feb 25;13:821133. doi: 10.3389/fphar.2022.821133. 
      eCollection 2022.